3 To Understand lucose Metabolism In Vivo, One must Understand Regulation by Muscle Muscle is ~90% of insulin sensitive tissue Muscle metabolism can increase ~10x in response to exercise Muscle is a major site of insulin resistance in diabetes

5 Outside Inside (-) lycogen Synthesis lc LUT4 LUT1 lc HK II lc 6-P lycolysis lucose is not officially taken up by muscle until it is phosphorylated. lucose phosphorylation traps carbons in the muscle and primes it for metabolism.

12 [ 3 H]2-deoxyglucose Sensitive Tissue specific 2-deoxyglucose metabolism may differ from that for glucose Usually single endpoint measure enerally not applied to people. Extracellular Water 2D 2D Intracellular Water 2D-P

22 Contraction- and Insulin-stimulated Muscle lucose Uptake use Separate Cell Signaling Pathways Contraction does not phosphorylate proteins involved in early insulin signaling steps. Wortmannin eliminates insulin- but not contractionstimulated increases in glucose transport. Insulin and contraction recruit LUT4 from different pools. Effects of insulin and exercise on glucose transport are additive. Insulin resistant states are not always contraction resistant.

52 Summary Extracellular Membrane Intracellular glucose glucose 6-phosphate Control of Muscle lucose Uptake is Distributed between lucose Delivery to Muscle, lucose Transport into Muscle, and lucose Phosphorylation into Muscle. Treatment of Insulin Resistance may Involve any one or More of the Three Steps

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